Intensive medical management of critically ill patients or patients undergoing operations which result in severe physiological disturbances requires detailed monitoring of the cardio-respiratory system. At present the apparati used to provide such monitoring frequently require insertion into the body. For example, a pulmonary artery catheter must be inserted through the skin, into a major vessel and passed along the vessel, through the heart chambers into the pulmonary artery. The use of such monitoring devices add their own morbidity and mortality to the patient's underlying illness. These risks must always be weighed against the possible benefit of the information gained.
A non-invasive monitor would be of great benefit in that it would decrease the discomfort and risk of added morbidity and mortality to patients already very ill. It would further have application where such test information is required but invasive techniques are unjustified (in ambulatory patients and athletes) or impossible to institute (small infants).
In the prior art there are several non-invasive methods of obtaining PvCO.sub.2. These methods are based on the principle of using the lungs as a chamber that comes into equilibrium with the partial pressure of a gas dissolved in a liquid, that is, an aerotonometer, whereby the lung gases are brought into equilibrium with the gases dissolved in the inflowing pulmonary artery blood. This equilibrium must be reached before recirculated blood with altered gas concentrations reaches the lungs.
One Method: Equilibrium by Breath-holding
This technique is reviewed in detail by Grollman (Grollman, A., The Cardiac Output of Man in Health and Disease. Charles C. Thomas 1932, p. 25-26). When a subject holds his breath, the partial pressure of carbon dioxide in the alveolar air (PACO.sub.2) gradually increases at a decreasing rate of increase as it approaches the PvCO.sub.2. Equilibrium is recognized by a constant PCO.sub.2 in several successive samples.
When room air is inhaled, the amount of CO.sub.2 that diffuses into the lungs is insufficient to equilibrate the PACO.sub.2 with the PvCO.sub.2 within a recirculation time of about twenty seconds. Grollman (Grollman, A., The Cardiac Output of Man in Health and Disease. Charles C. Thomas 1931 p. 28) describes a method where before breath-holding the subject inspire a gas containing a concentration of CO.sub.2 determined by trial and error to give a constant PCO.sub.2 on successive expiratory samples.
Dubois et al. (Dubois, A. B., Britt, A. G., Fenn, W. O.; Alveolar CO.sub.2 During the Respiratory Cycle. Jour. App. Physical 4:535 1952) have demonstrated that the rise of CO.sub.2 during breath-holding can be accurately approximated by a single exponential. Frankel et al. (Frankel, D. Z. N., Sandham, G., Rebuck, A. S.; A noninvasive Method for Measuring the PCO.sub.2 of Mixed Venous Blood. American Rev. Resp. 0.5 117:63, 1978) describe a technique where the patient breath-holds either 100% O.sub.2 or 12% CO.sub.2 in O.sub.2. The subject's breath was held in inspiration by an occlusive solenoid valve controlled manually by the investigators. At the end of five seconds and ten seconds, a 500 ml sample of expired gas was collected and analyzed. Using a formula similar to Dubois, the PvCO.sub.2 was calculated by extrapolating the points to an asymptote which is claimed to represent the PvCO.sub.2. Frankel, Sandham and Rebuck (Frankel, D. Z. N., Sandham G., Rebuck A. S.; A New Method for Measuring PCO.sub.2 During Anesthesia, Br. v. Anaesth, 51, 215, 1979) used a similar technique on unconscious patients during anesthesia.
These breath-holding techniques have a number of serious drawbacks.
(1) They require patient co-operation. PA1 (2) They are difficult for the patient to perform. Sick patients with respiratory disease are usually unable to take a breath consisting of 2 liters or more as required by the technique. They are seldom able to hold their breath in deep inspiration as required. This is especially true of Frankel's technique where inhalation of 12% CO.sub.2 is required. PA1 (3) Even if the manoeuver is performed, it alters the very parameters one is trying to measure: The cardiac output, PvCO.sub.2, and even the systemic arterial PO.sub.2 (PaO.sub.2). PA1 (4) Performance of the manoeuver may harm the patient by dropping his cardiac output, causing hypoxia and hypercarbia. PA1 (5) The data obtained is difficult to analyze. Fitting exponential curves to two points and extrapolating to an asymptote introduces mathematical difficulties and uncertainties to the measured variable. The cumbersomeness of the described methods illustrates why they cannot be used routinely in the clinical setting and why full automation has not been achieved. PA1 (1) They are very cumbersome requiring a large amount of manipulation of equipment. The rebreathing container must be filled to a critical size and CO.sub.2 partial pressure, which may be different for each patient. Powles (Powles, A. C. P., Campbell, E. J. M.; An Improved Rebreathing Method for Measuring Mixed Venous CO.sub.2 Tension and Its Clinical Application. Can. Med. Ass. Jour. 118:508, 1978.) and Franciosa (Franciosa J. A.; Evaluation of the CO.sub.2 Rebreathing Cardiac Output Method in Seriously Ill Patients. Circulation 5:5(3): 449, 1977) say they go through the test five to six times before the appropriate combination can be found. PA1 (2) The patient is required to perform manoeuvers. Franciosa'a patients must take deep breaths and breathe to a metronome. PA1 (3) Data is difficult to interpret. Powles, in discussing his end point plateau, illustrates three separate plateaus To pick the appropriate one requires considerable expertise and may in fact be impossible. Its use on ventilated patients has not yet been described. These drawbacks preclude widespread routine clinical use or automation. PA1 (1) whereby the patient need not hold his breath, rebreathe or provide prolonged exhalations, PA1 (2) that is independent of the patient's tidal volume, respiratory frequency or pattern of ventilation, PA1 (3) that works equally well in intubated and mechanically ventilated patients as it does in those breathing spontaneously, PA1 (4) that does not require a change in the patient's inspired oxygen concentration, PA1 (5) from data that can be plotted on linear curves, PA1 (6) where the mathematics is therefore readily understandable and the end point is easily calculated, and PA1 (7) automatically with minimal manipulation of hardware and no operator-performed data analysis or calculations. PA1 (a) measuring the PCO.sub.2 of the gases inhaled and exhaled by the patient under control conditions without rebreathing; PA1 (b) causing the patient to inhale a test gas containing at least a small concentration of CO.sub.2 and continuing to measure the PCO.sub.2 of the inspired and expired gases (the patient taking at least two breaths and preferably three or four breaths of the test gas without rebreathing); PA1 (c) determining the PCO.sub.2 of the inspired gases (P.sub.I CO.sub.2) and the end tidal PCO.sub.2 of expired gases (PECO.sub.2); PA1 (d) determining the difference between the end tidal PCO.sub.2 and inspired PCO.sub.2 under control and test conditions (in the test conditions preferably after inhaling the third or fourth breath of a test gas), and relating it to the inspired PCO.sub.2 used in the determination of the difference. PA1 (e) This relationship is linear. Any two points relating PECO.sub.2 -P.sub.I CO.sub.2 to P.sub.I CO.sub.2, will define a straight line. This line can be determined mathematically including graphically by using at least two points generated as described in sub-paragraphs (a) to (d) inclusive. The PICO.sub.2 calculated using this relation yields PvCO.sub.2 when PECO.sub.2 -PICO.sub.2 =0. PA1 (a) means for measuring the PCO.sub.2 of the gases inhaled and exhaled by the patient under control conditions without rebreathing, PA1 (b) means for permitting the patient to inhale a test gas containing at least a small concentration of CO.sub.2 without rebreathing and means for measuring the PCO.sub.2 of the inspired and expired gases that result from breathing the test gases (preferably including means for controlling the number of breaths of test gas taken, for example three or four), PA1 (c) a reservoir for the inhaled test gases containing at least a small concentration of CO.sub.2. PA1 (i) a manifold having ports therein one port for communicating with the mouth of the patient, another port for permitting exhaled gases to escape to the atmosphere, another port for permitting entry of the test gas from the reservoir to the manifold and another port to permit entry of room air to the manifold for inhalation; PA1 (ii) two one-way valves, one such valve positioned in the manifold between the exhalation port and the port leading to the reservoir to permit control gas and test gas to pass therethrough but preclude any exhaled gases from passing through it and the other such valves being positioned at the exhalation port permitting exhalation but precluding entry of room air during inhalation, PA1 (iii) a three-way valve in the manifold for alternately allowing control condition gas or test gas to pass through the port for communicating with the mouth of the patient.
Another Method of Non-Invasively Obtaining PvCO.sub.2 :
Equilibration by Rebreathing
Rebreathing is conceptually very similar to breath-holding. In breath-holding, the lungs act as a closed in which the PCO.sub.2 rises as a decreasing exponential towards the PvCO.sub.2. With rebreathing, the closed space is expanded to include a container attached to the lungs in which the gases are mixed by passing the gas back and forth between the container and the lung. Even to a greater extent than with the breath-holding, the amount of CO.sub.2 entering the closed system is insufficient to effect an equilibrium with the mixed venous PCO.sub.2 within a blood recirculation time.
The rise in PCO.sub.2 in the closed system with time is also exponential. Defares (Defares, J. G. Determination of PVCO.sub.2 From the Exponential CO.sub.2 Rise Rebreathinq, Appl. Physiol. 13 (2): 159-164, 1958) used repeated or constant sampling of PCO.sub.2 as gas is rebreathed from the container to extrapolate to a final equilibrium PvCO.sub.2 value.
Others have employed various techniques to add an amount of CO.sub.2 to the rebreathing container that would result in a constant PCO.sub.2 in the closed system, indicating equilibration with PvCO.sub.2. These are reviewed in more detail by Grollman (Grollman, A. The Cardiac Output of Man in Health and Disease. Charles C. Thomas, 1932 pg. 17-25) and Richards and Strauss (Richards, D. W. Jr., Strauss, M. L., Carbon Dioxide and Oxygen Tensions of the Mixed Venous Blood of Man at Rest. J. Clin Investig, 9:475, 1930). Douglas and Haldane (Douglas C. G., Haldane J. S.; The Regulation of the General Circulation Rate in Man.J. Physiol 56:69, 1922) filled a bag with 6.5%-10% CO.sub.2, rebreathed its contents twice, then performed a breath-holding manoeuver. In 1922 Meakins and Davies rebreathed into a container for about twenty seconds, rested and again rebreathed into repeated until the PCO.sub.2 in the container was constant. More recently Collier (Collier, C. R., Determination of Mixed Venous CO.sub.2 Tensions by Rebreathing. J. App Physiol 9:25, 1956.) described a technique using rebreathing and monitoring of inspired and expired PCO.sub.2 using a device for continous measuring CO.sub.2 (or a capnograph). By trial and error, the appropriate initial partial pressure of CO.sub.2 (or PCO.sub.2) of the rebreathing container is found for a particular patient. He then rebreathes from this container. Before one blood recirculation time, an equilibrium may be established with the PvCO.sub.2 as indicated by a plateau of the capnograph tracing. Powles and Campbell (Powles A. C. P., Campbell, E. J. M.; An Improved Rebreathing Method for Measuring Mixed Venous CO.sub.2 Tension and its Clinical Application. Can. Med. Ass. Jour. 118:501, 1978) outlined this application of the technique to the clinical setting and characterized further the appropriate capnograph equilibrium plateau. Franciosa (Franciosa, J. A.; Evaluations of the CO.sub.2 Rebreathing Cardiac Output Method in Seriously Ill Patients. Circulation 55(3): 449, 1977) also describes the clinical application of the rebreathing technique.
Rebreathing techniques have a number of serious shortcomings.
Another Method of Non-Invasively Obtaininq PvCO.sub.2, Prolonged Exhalation
Kim et al (Kim, T. S., Rahn, H., Farhi, L. E.; Estimation of True Venous and Arterial PCO.sub.2 by Gas Analysis of a Single Breath. J. Appl. Physiol 21(4):1338, 1966) describe a method for arriving at the PvCO.sub.2 from a single breath. The subject must take a deep breath of ambient atmosphere and exhale over ten or more seconds. Kim et al continuously monitor PO.sub.2 and PCO.sub.2. They use the relative values of PO.sub.2 and PCO.sub.2 to predict PvCO.sub.2.
This technique again has the drawback that it requires a critical patient manoeuver. It has not been used in ventilated or ill patients. Its theory and application is difficult. It therefore does not lend itself to automation or manual application in the clinical situation.
As stated by Grollman (Grollman A., The Cardiac Output of Man in Health and Disease. Charles C. Thomas, 1932, pg. 17-25), the techniques for determination of PvCO.sub.2 "consist, for the most part, of various rebreathing procedures or procedures involving more complex respiratory gymnastics" such as breath-holding and prolonged exhalations.
It is therefore an object of this invention to provide a method and apparatus whereby PvCO.sub.2 can be obtained, non-invasively while the patient continues to breathe in his/her usual manner.
It is a further object of this invention to provide a method and apparatus where PvCO.sub.2 can be obtained:
Further and other objects of the invention will be apparent to a man skilled in the art from the following summary of the invention and detailed description of the embodiments.